The purposes of this proposal are to describe the effects of hypoxia and increased lung volume, alone and in combination, on the rate of fluid filtration from the blood vessels to the interstitium of the lung. We will determine whether these effects are caused by alterations in the pressure gradient for filtration or by alterations of the permeability or area of the vascular-interstitial interface. Because of its great significance with respect to the effects of hypoxia on lung fluid filtration, the major site of hypoxic vasoconstriction will be localized to arteries, veins, or alveolar vessels. The species and age-dependency of the hypoxic influence on fluid transport will be determined and correlated with the reactivity of the pulmonary vasoconstrictor response to hypoxia, which is known to vary with species and age. We will determine whether steady-state lung weight gain, measured under conditions of constant blood flow and pulmonary artery and left atrial pressures, is an accurate index of the rate of fluid filtration, as has been frequently assumed in past studies utilizing isolated lung preparations, or whether this measurement is also significantly influenced by lung lymph flow or slow changes in intravascular volume. Finally, we will determine the applicability of our isolated lung data to intact animals. It is hoped that our results will lead to a greater understanding of the mechanism of high altitude pulmonary edema and to improved management of patients with pulmonary edema of other etiologies, since these patients are hypoxic and are frequently subjected to therapeutic maneuvers designed to increase lung volume.